The purpose of this program is a broadly-based, multidisciplinary, long-term basic and clinical comparative investigation of the structural, contractile and metabolic characteristics of normal and diseased muscle with the aim of identifying and characterizing those pathophysiologic events which are most likely to result in abnormal muscle structure and function. The ultimate goal is the elucidation of the mechanisms basic to muscle diseases and to identify methods for alleviating, treating or preventing these disorders. These investigations represent a spectrum of interrelated studies carried out in a horizontal plane at several biological levels. In a vertical plane, the spectrum includes multiple interspecies comparisons. The studies are organized within four complementary sections supported by experimental animal, clinical and administrative cores. Both the basic and clinical research programs, built around a research team of proven competence, are focused on a range of problems relevant to related diseases (myopathies) and disciplines (muscle biology). There is, therefore, a coherent realistic central focus, clearly defined goals clearly specified appraoches for attaining these goals. The project also provides a strong base for training as well as for research.